ABSTRACT This is an application for a Mentored Patient-Oriented Research Career Development Award (K23) to support the academic career development of the applicant. The candidate's long term goal is to become an independent clinical investigator and national leader in the study of anxiety and substance use comorbidity among groups prone to health disparities, with a particular emphasis on bidirectional and dynamic influences of anxiety and alcohol abuse among Hispanics/Latinos. The applicant has conducted research focused on the development of anxiety disorders across the lifespan, including their association with substance use outcomes. This application builds on the applicant's expertise in the area of anxiety and follows a logical, but novel, progression from prior research and training experiences to the development of a new area of expertise in alcohol-anxiety comorbidity in a health disparities population. The application proposes training experiences that are necessary for the next step in this research program, including advanced training in psychopharmacology of drugs of abuse; health disparities; advanced statistical methods; and grant writing and science dissemination skills. The mentorship of a select group of senior investigators will foster the candidate's development in a promising new area of research. The goals of the proposed study are to examine (1) the pharmacological and expectancy mechanisms implicated in the acute anxiety effects of alcohol, (2) the covariation between acute anxiety effects of alcohol and anxiety- induced motivation to consume alcohol, and (3) sociocultural (perceived racial discrimination) influences in these outcomes in a sample of moderate-to-heavy drinking adult Hispanics/Latinos ages 21-65. This approach is novel in that it aims to examine several complex alcohol-anxiety associations among Hispanics/Latinos in one overarching model, which has yet to be attempted in a human experimental paradigm. This proposal is conceptualized as a prototypical example of cross-disciplinary translational research that can explicate mechanisms from a multi-method framework to enhance our understanding of complex anxiety-alcohol relations, and serve as a catalyst for future work in this emerging domain among a group prone to health disparities. The proposed study will use rigorous methods of assessment to address three primary aims: 1) to test the pharmacological and expectancy effects of acute alcohol stress dampening, 2) to test anxiety a proximal antecedent of urge to drink and ad lib alcohol consumption, and 3) to test associations between perceived racial discrimination and Aim 1 and 2 outcomes in a large sample of Hispanics/Latinos. The training and research outlined in this proposal will equip the candidate with a unique set of necessary skills to advance knowledge in this important yet understudied area. Over the long-term, data from this study will enhance understanding of the mechanisms involved in the alcohol-anxiety connection among Hispanics/Latinos and will directly inform and strategically guide the development of novel treatments for health disparities populations.